tbuckley/cabot-search huggingface dataset:
Anlotinib combined with pemetrexed and carboplatin as first-line treatment in driver-gene negative advanced non-squamous non-small cell lung cancer: ALTER L012.
Authors: Qiming Wang, Zhen He, Xiuli Yang, Tianjiang Ma, Qiumin Yang, Chenghui Zhang, Yunfang Chen
Journal: Journal of Clinical Oncology (2022)

e21147 Background: Anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients. The study aimed to explore the efficacy and safety of anlotinib combined with carboplatin and pemetrexed followed by anlotinib combined with pemetrexed maintenance in advanced EGFR/ALK wild-type non-squamous non-small-cell lung cancer (nsq-NSCLC). Methods: This multicenter (n = 6), single-arm clinical trial recruited patients with wild-type EGFR/ALK advanced nsq-NSCLC who received first-line therapy between March 2019 and February 2021. Patients received anlotinib (12 mg p.o., QD d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m, iv, d1, Q3W) + carboplatin (AUC = 5, iv, d1, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints are OS, objective response (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Feb 2021, 44 patients were enrolled and 38 of them have received at least one tumor assessment. The median age was 62 (range: 33-75) years. Most of the patients were non-smoker (68.4%). The median follow-up was 13.6 (range: 12.3-14.9) months. Median PFS was 10.5 (95%CI: 4.1, 17.0) months, and median OS was 23.4 (95%CI: NE, NE) months. The DCR and ORR were 94.7% and 60.5%, respectively. Twelve participants had treatment-related adverse events (TEAEs) of grade &gt; 3. The most common Grade 3 AEs were hypertension (23.7%), neutropenia (19.4%), and bone marrow hypocellular (10.5%). Seven patients discontinued treatment, including two during induction and five during maintenance. No grade 5 TRAE was recorded. In the non-smoker participants, the median PFS was 14.5 (95%CI: 4.0-25.0) months. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin followed by anlotinib plus pemetrexed maintenance therapy might be a promising treatment for patients with wild-type EGFR/ALK advanced nsq-NSCLC. The combination was well tolerated, and the AEs were manageable. Clinical trial information: NCT03790228.
Stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with small cell lung cancer (SCLC) and intracranial metastatic disease (IMD): A systematic review and meta-analysis.
Authors: Karolina Gaebe, Alyssa Y. Li, Amy Park, Ambika Parmar, Benjamin H. Lok, Arjun Sahgal, Kelvin K. Chan, Anders W. Erickson, Sunit Das
Journal: Journal of Clinical Oncology (2022)

8570 Background: Patients with SCLC are at high risk for the development of IMD and, subsequently, rapid intracranial progression. SRS has supplanted WBRT as first-line treatment for IMD in most solid cancers, but WBRT remains first-line treatment for IMD in SCLC patients. Data on SRS in SCLC are limited to small retrospective studies. Methods: Studies reporting on SRS in SCLC patients with IMD were collected from EMBASE, MEDLINE, CENTRAL, and grey literature sources (n = 3,732 studies). Random-effects meta-analysis pooled hazard ratios (HR) for overall survival (OS) between SRS and WBRT ± SRS boost, as well as medians for OS in months (mo) and risk rates for intracranial local (LC) and intracranial distant control (DC) in single-arm SRS studies. Results: OS following SRS was non-inferior compared with WBRT ± SRS boost (HR 0.90; 95% confidence interval (95CI), 0.73-1.10; n = 7 studies; n = 18,130 patients), and superior compared with WBRT alone (HR 0.80; 95CI, 0.66-0.96; n = 7 studies; n = 16,961 patients). Pooled median OS from single-arm studies following SRS was 8.99 mo (95CI, 7.86-10.15; n = 14 studies; n = 1,682 patients). Pooled LC and DC estimates following SRS were 81% (95CI, 67%-99%) and 66% (95CI, 50%- 86%), respectively, at 6 mo, and 78% (95CI, 61%-98%) and 58% (95CI, 46%-75%), respectively, at 12 mo. Conclusions: This systematic review and meta-analysis provides evidence that SRS may achieve analogous survival outcomes compared with WBRT in patients with SCLC and IMD, indicating that a subset of SCLC patients may benefit from first-line SRS treatment. Prospective trials should investigate the impact of metastatic burden as well as LC and DC differences between WBRT- and SRS-treated SCLC patients.
SNS-101, a highly selective monoclonal antibody against the active form of VISTA, demonstrates significantly reduced cytokine release.
Authors: Edward van der Horst, Zhi-Gang Jiang, Kanam Malhotra, Arnab Mukherjee, Zuzana Biesova, Anokhi Cifuentes, Thomas Thisted, Robert Hamilton Pierce, Gaëlle Martin, Kader Thiam
Journal: Journal of Clinical Oncology (2022)

e14504 Background: Active cancer immunotherapeutics frequently give rise to immune-mediated adverse events (AEs), including cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). On-target, off-tumor activation of myeloid lineage cells (e.g. monocytes) has been implicated as a factor in the generation of these immune-mediated AEs. VISTA (V-domain Ig suppressor of T-cell activation) is an immune checkpoint, which is highly expressed on myeloid cells, and binds PSGL-1 on T-cells, but only when ‘activated’ by protonation at low pH (̃pH 6). Inhibition of the VISTA:PSGL-1 interaction in the acidic tumor microenvironment has been shown to be efficacious in multiple syngeneic murine tumor models. However, antibodies binding to VISTA at physiological pH 7.4 have significant potential to induce dose-limiting toxicities such as CRS and/or ICANS and be prematurely eliminated from circulation through targeted-mediated drug disposition (TMDD), reducing the likelihood of reaching efficacious drug occupancy levels. Among several non-pH-selective antibodies in clinical development, JNJ-61610588 (now CI-8993) induced dose-limiting on-target CRS at subtherapeutic dose levels and exhibited TMDD. To mitigate potential CRS and prevent TMDD, we developed SNS-101, a highly selective monoclonal IgG1 antibody for “active” VISTA, which inhibits the critical interaction with PSGL-1. Methods: Using flow cytometry at physiological pH, we compared SNS-101 with clinical stage non-pH-selective anti-VISTA antibodies and examined binding to VISTA-positive cell populations in human PBMCs as well as in human CD34+ cord blood cells reconstituted BRGSF-HIS mice (humanized BRGSF-HIS mice), which develop both human lymphoid and myeloid compartments. Furthermore, we performed in vitro and in vivo CRS studies in a HUVEC/PBMC co-culture system and humanized BRGSF-HIS mice, respectively. Results: Under physiological pH, non-pH-selective antibodies bound to monocytes, neutrophils and NK cells whereas SNS-101 did not exhibit any significant interactions. CRS assays indicate that the magnitude of induced cytokine levels was significantly higher with non-pH-selective antibodies compared to SNS-101. Conclusions: We assessed the binding profile of SNS-101 vs. non-pH-selective VISTA antibodies. Our results demonstrate that SNS-101 does not bind to VISTA-positive cells in circulating blood. In addition, in vitro and in vivo CRS studies suggest that SNS-101 has a lower risk of inducing CRS compared to non-pH selective anti-VISTA antibodies, alleviating liabilities previously associated with anti-VISTA antibodies. IND-enabling studies, including pharmacokinetic and toxicology studies, are ongoing.
Socioeconomic factors associated with a late-stage pancreatic cancer diagnosis: An analysis of the national cancer database.
Authors: Jillian Marie Gallegos, Kiana Verplancke, Alexandra Taylor, Kevin McMahon, Peter T. Silberstein, Mary Elizabeth Dahl
Journal: Journal of Clinical Oncology (2022)

4135 Background: Pancreatic cancer is an aggressive, lethal cancer that is the 4 th leading cause of cancer death in the United States. It is often asymptomatic until later stages, thus it is critical to assess the socioeconomic factors associated with diagnosis at early vs. late stages. Using the National Cancer Database, we aim to identify associations between socioeconomic factors of patients that present with early stage (0-I) pancreatic cancer in comparison to late-stage disease (stage IV) at diagnosis. Methods: In this study, 256,822 patients from the National Cancer Database who were diagnosed with NCDB Analytic Stage Group stage 0-I and stage IV pancreatic cancer were analyzed based on age, race, sex, ethnicity, insurance type, income, geographic location, education and Charlson-Deyo score. Demographic factors of patients that presented with early and late-stage disease were analyzed using chi square and multivariate analysis. All patients included in the study were diagnosed with pancreatic cancer between 2004 and 2018. Results: We identified significant ( P &lt;0.05) associations between race, sex, insurance status, education, income, and geographic location with diagnosis of advanced-stage disease. A greater percentage of males were diagnosed with late-stage cancer than early-stage (52.8% vs 47.9%). Females were more likely to have an earlier-stage diagnosis and were 15% less likely to have late-stage diagnosis than males (p &lt; 0.001 and 95% CI = 0.839-0.875). African Americans were 10% more likely to have a late-stage diagnosis than Caucasians (p &lt; 0.001 and 95% CI = 1.069-1.144). For insurance status, private and Medicaid insurance had higher percentages of late-stage diagnosis than early-stages, and all types of insurance had lower rates of late-stage diagnosis than patients without insurance (p &lt; 0.001). Patients from a zip-code associated with &lt; $38,000 median household income and zip-codes with lower levels of high school diplomas had higher rates of late-stage diagnosis (p &lt; 0.025). Conclusions: Factors associated with increased likelihood of pancreatic cancer presentation at advanced stage compared to early stage include race, sex, insurance status, education, median income, comorbidity score, and geographic location.
A phase II study of CPX-351 in younger patients &lt; 60 years old with secondary acute myeloid leukemia: Trial in progress.
Authors: Mahesh Swaminathan, Salman Fazal, Elizabeth A. Griffiths, James E. Thompson, Pamela Jeannette Sung, Steven Daniel Green, Emily Li, Meriem Said, Krista Belko, Emmalyn Mattice, Kristopher Attwood, Eunice S. Wang, Amanda Przespolewski
Journal: Journal of Clinical Oncology (2022)

TPS7073 Background: Patients (pts) with secondary acute myeloid leukemia (s-AML) and therapy-related AML (t-AML) have poor long-term outcomes following standard induction 7+3 chemotherapy. CPX-351, a liposomal formulation of cytarabine and daunorubicin fixed at the synergistic ratio of 5:1, is indicated for the treatment of pts with newly diagnosed s-AML and t-AML based on the results of a phase III trial favorably comparing CPX-351 to 7+3. Although the trial only enrolled pts aged 60-75 years (Y), CPX-351 is approved by the United States Food and Drug Administration for all adult pts with t-AML and AML with myelodysplasia-related changes (AML-MRC). In a prior retrospective analysis of CPX-351 in pts &lt;60 Y with s-AML, we noted that the outcomes of these younger pts appeared inferior to those reported in older pts (60-75 Y) in the phase III trial (Przespolewski et al. Blood 2018 p.2677). Therefore, we designed this prospective study to evaluate the efficacy of CPX-351 in pts &lt;60 Y with untreated s-AML and t-AML. Methods: In this phase II single-arm multi-institutional study, pts aged 18-59 Y with untreated t-AML or AML-MRC, adequate organ function, and ECOG performance status ≤ 2 are eligible. Pts with active central nervous system disease and infections were excluded. CPX-351 will be dosed at 100 mg/m 2 cytarabine and 44 mg/m 2 daunorubicin on days 1, 3, and 5 during induction. Bone marrow biopsy will be performed between days 14-21 to assess response. If needed, re-induction CPX-351 dose will be 44 mg/m 2 daunorubicin/100 mg/m 2 cytarabine on days 1 and 3. Pts achieving a complete remission (CR) following induction can receive up to 2 cycles of consolidation CPX-351 dosed as cytarabine 65 mg/m 2 and daunorubicin 29 mg/m 2 on days 1 and 3. The primary endpoint of the study is overall response rates defined as CR and CR with incomplete blood count recovery (CRi)) within 45 days of beginning therapy. Secondary endpoints are duration of response, event-free survival, overall survival, rate of allogeneic stem cell transplant, and adverse events. A maximum of 46 pts will be enrolled at 4 U.S. sites with 5-year follow-up from the start of CPX-351.The study is open and has enrolled 4 pts to date. Clinical trial information: NCT04269213.
Early detection of hepatocellular carcinoma using cfDNA signatures from cirrhotic patients with nodules.
Authors: Rong Fan, Lei Chen, Yingchao Wang, Weiwei Wei, Yunsong Qian, Lutao Du, Xiaotang Fan, Yanlong Yu, Guoqing Jiang, Yangqing Huang, Honglian Bai, Yanhang Gao, Chunying Wang, Guohong Deng, Qingzheng Zhang, Chuanxin Wang, Jingfeng Liu, Hongyang Wang, Jinlin Hou
Journal: Journal of Clinical Oncology (2022)

4113 Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Early detection of HCC patients is related to favorable survival. Nodules in liver cirrhosis (LC) are at higher risk of developing into HCC. There is an urgent clinical need for development of an accurate and affordable non-invasive method for early HCC diagnosis among LC patients with nodules. Methods: We have previously shown that the genome-wide HIFI (5-Hydroxymethylcytosine/motIf/ Fragmentation/nucleosome footprInt) method held a solid diagnostic value in differentiating HCC from LC. In this study, we leverage this knowledge to diagnose early HCC (BCLC 0/A) in cirrhotic nodules using copy number variation (CNV) to replace 5-Hydroxymethylcytosine to simplify NGS protocol and decrease cost. The updated method generates a score that reflects the presence of tumor-derived cfDNA in 10 ml blood via low coverage (2x) whole-genome sequencing (WGS). We applied it in a retrospective cohort (validation set 1, n = 171) and a prospective cohort (validation set 2, n = 156), both of which involved patients with newly diagnosed early stage HCC (BCLC 0/A) as well as individuals with cirrhotic nodules. Results: The updated method showed excellent performance for early HCC detection both in the validation set 1 (84 HCC and 87 cirrhotic nodules; AUC: 0.951, 82.1% sensitivity at 90.8% specificity) and validation set 2 (71 HCC and 85 cirrhotic nodules; AUC: 0.958, 81.7% sensitivity at 91.8% specificity) (Table). The AUC values for distinguishing early HCC from cirrhotic nodules could reach 0.951 (80.9% sensitivity at 91.0% specificity) and 0.947 (74.7% sensitivity at 92.1% specificity) among patients with AFP &lt; 400 μg/L and those with nodular size &lt; = 2 cm, respectively. More importantly, our model also maintained consistent performance in detecting very early stage HCC (BCLC 0) with AUC of 0.941 (74.7% sensitivity at 91.3% specificity). Conclusions: These findings provide an accurate, affordable, excellent clinical potential model integrating four cfDNA molecular signatures for detecting early stage HCC from cirrhotic nodules using low-coverage WGS of plasma cfDNA samples. [Table: see text]
A feasibility study of remote patient monitoring among vulnerable patients with cancer.
Authors: Alaina J Kessler, Melanie Besculides, Carol Kisswany, Mark Liu, Asem Berkalieva, Madhu Mazumdar, Cardinale B. Smith, Ksenia O. Gorbenko
Journal: Journal of Clinical Oncology (2022)

e13652 Background: Patients with cancer have high rates of healthcare utilization due to complications of disease and treatment. Early identification of patient illness may help reduce acute care use and improve quality of care. Remote patient monitoring (RPM), a type of telemedicine involving collection and transmission of health data from a patient’s home to clinicians, has promise to alleviate disparities by providing timely access and early intervention, particularly during the COVID-19 pandemic. Studies of digital interventions in oncology have demonstrated reduction in symptom distress and unplanned hospitalizations but lack focus on minority patients whereas studies of telehealth aiming to address disparities have not focused on patients with cancer. In this pilot study, we aimed to evaluate the feasibility of RPM among patients with cancer at a large urban medical center serving a racially and socioeconomically diverse population. Methods: We partnered with a secure HIPAA-compliant platform and FDA-approved RPM device, Current Health, which monitored heart rate, temperature, respiration, oxygen saturation, and blood pressure. The kit included broadband access and a tablet to provide telehealth services. Oncology Clinicians determined clinical inclusion and exclusion criteria of RPM initiation for patients on the bone marrow transplant service and patients with myeloma and lung cancer. A centralized team of Nurse Practitioners (NPs) monitored alarms. Clinical alarms indicated abnormal vital signs; technical alarms indicated no data transmission for a 12-hour period. We measured feasibility by recruitment and retention, and used descriptive statistics to describe the study population, time enrolled on RPM, and alarms. Results: To date, we enrolled 30 patients on the RPM platform over a 10-month period with a weekly census of 9-10 patients undergoing RPM monitoring. Of the 30 patients, 17 (57%) were white, 7 (23%) Black, and 2 (7%) Asian; 2 patients (7%) identified as Hispanic. The average age was 57.4 years. The majority of patients (93%) had hematologic malignancies, all of whom were enrolled on hospital discharge. Of the 2 patients with lung cancer, 1 patient was enrolled from the outpatient setting and 1 following hospital discharge. The mean length of time per patient enrolled with the device was 21.7 days. Over 10 months, there were 393 technical and 62 clinical alarms with an average of 3 clinical alarms per week addressed by NPs by phone, indicating low clinician burden. Conclusions: This pilot study demonstrated the feasibility of RPM monitoring in patients with cancer. Future studies should evaluate patient-reported and healthcare utilization outcomes, as well as barriers to reimbursement. The identification of best practices in telemedicine implementation can accelerate adoption and increase high quality, timely, and equitable cancer care.
Anti-neoplastic drugs for malignant pleural effusion in non-small cell lung cancer: A meta-analysis.
Authors: Obada Ehab Ababneh, Sebawe Syaj, Yaman Belal Ahmed, Zaid Hatamleh, Sara Saleh, Alaa Zaitoun, Marah Akhdar, Mohammad Alsaid Ahmad, Raghad Al-shdaifat, Shadi Hamouri
Journal: Journal of Clinical Oncology (2022)

e21060 Background: Malignant pleural effusion (MPE) occurs in 7-23% of advanced non-small cell lung cancer (NSCLC) patients with overall survival (OS) of 8.5 months only. The optimum anti-neoplastic regimen in MPE is yet to be determined. Thus, we conducted a meta-analysis to determine the optimum anti-neoplastic agent in managing MPE in NSCLC. Methods: We searched PubMed, Scopus, CENTRAL, ASCO, ESMO, and IASLC meetings libraries to retrieve relevant trials. We included single-arm and controlled trials in which patients with MPE were treated by anti-neoplastic drugs such as chemotherapy and/or targeted therapy. Patients treated with radiotherapy were excluded. Primary and secondary endpoints were efficacy and safety, respectively. Meta-analysis was conducted for the primary endpoint estimated by OS and objective response rate (ORR). In addition, subgroup analysis was conducted to investigate the effect of route of administration (ROA) and randomization on ORR. Results: We included 11 trials with a total of 542 patients. There were 5 randomized clinical trials, 5 phase II trials, and 1 phase I trial with a total of 16 relevant arms. Five arms used single-agent chemotherapy (SC), 11 combined therapy (CT) and 6 arms bevacizumab-based (BEVA) therapy. The ROA was intrapleural (IP) in 10 arms and intravenous (IV) in 6 arms. We pooled 124 patients from 5 trials that reported ORR results for SC patients. The pooled ORR was 41.7% (95% CI: 32.8 to 50.8%) with no heterogeneity ( I 2 = 0%, p = 0.47). Pooling of 396 patients who underwent CT in 10 studies results in an ORR of 64.1% (95% CI: 52.7 to 74.8%) with a high heterogeneity rate ( I 2 = 84%, p&lt; 0.01). Analysis of BEVA studies yielded an ORR of 62.2% (95% CI: 43.5 to 79.2%), representing 133 patients from 5 trials. The table shows the effect of randomization and ROA on ORR. One-year OS was reported in 4 studies that used CT; pooled 1-year OS estimate for 216 patients was 81.2% (95% CI: 75.5 to 86.4%). As for grade 3/4 AEs, the occurrence of nausea/vomiting (N/V) was higher in CT than SC (14% vs 2%). Chest pain rate was similar (9.8% vs 7.0%), leukopenia was higher in BEVA than SC (19.1% vs 9.8%), and neutropenia was more prevalent in BEVA than CT (22.1% vs 8.1%). Incidence of any-grade N/V was more common in BEVA than SC (42.9% vs 19.3%). Conclusions: Both CT and BEVA-based regimens were effective and safe in treating MPE. IP was superior to IV in CC and BEVA based regimens. ORR was higher in randomized trials, suggesting a better response of MPE under optimum clinical conditions. Further trials of these agents are needed to confirm these results.[Table: see text]